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The Effect of Intravenous and Intrathecal Morphine Preconditioning on Hepatic Ischaemia-Reperfusion Injury in Normal and Cirrhotic Livers

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The Effect of Intravenous and Intrathecal Morphine Preconditioning on Hepatic Ischaemia-Reperfusion Injury in Normal and Cirrhotic Livers

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The Effect of Intravenous and Intrathecal Morphine Preconditioning on Hepatic Ischaemia-Reperfusion Injury in Normal and Cirrhotic Livers by Yuan Wang
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This dissertation, "The Effect of Intravenous and Intrathecal Morphine Preconditioning on Hepatic Ischaemia-reperfusion Injury in Normal and Cirrhotic Livers" by Yuan, Wang, 王苑, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Hepatic ischaemia-reperfusion injury occurs when patients undergoing liver operations such as liver transplantation, tumour resection and shock. Intravenous and intrathecal administration of morphine can be used to provide analgesia prior or after liver surgery. It has been reported that systemically administered morphine conferred protective effect on numerous organs, including heart, brain and kidney. The focus of my research is to investigate the effect of intravenous and intrathecal morphine preconditioning on normal and cirrhotic livers. Further, PI3K/Akt, STAT3 and HO-1/iNOS pathways had been shown to ameliorate hepatic ischemia-reperfusion injury. Hence, we aim to investigate these possible signaling pathways associated with morphine mediated hepato-protection. A partial hepatic ischaemia reperfusion injury model in rats was used. The experiments were divided into two series: one involved in normal livers and the other one involved in cirrhotic livers. For the normal livers, morphine at different doses were administrated intravenously or intrathecally prior the onset of ischaemia, and the experiments were repeated with previous intravenous administration of naloxone methiodide (opioid receptor antagonist), or wortmannin (Akt inhibitor), respectively. For the cirrhotic livers, morphine at optimal doses were injected intravenously or intrathecally prior the onset of ischaemia. Those rats with only induced hepatic ischaemia-reperfusion injury only were marked as control groups. The effect of morphine preconditioning on hepatic architecture, apoptosis and liver function were evaluated respectively by hematoxylin-eosin (H&E) staining, Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) staining, the expression of cleaved Caspase-3, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the expression of phosphorylated Akt, phosphorylated JAK2, phosphorylated STAT3, HO-1 and iNOS were detected by Western Blot to determine the signaling pathways involved by intravenous and intrathecal morphine preconditioning. The normal livers series presented intravenous and intrathecal morphine preconditioning at the 100μg/kg, 10μg/kg, respectively, better persevered hepatic architecture when compared with control groups. The degree of liver cell apoptosis and expression of cleaved caspase-3 were also reduced by intravenous and intrathecal morphine preconditioning. In additional, intravenous and intrathecal morphine preconditioning ameliorated hepatocellular damage by reducing ALT&AST release. Moreover, the expressions of phosphorylated Akt and its downstream protein STAT3 were significantly increased by intravenous and intrathecal morphine preconditioning, compared with their respective control groups. The hepato-protective effect of intravenous and intrathecal morphine preconditioning was reversed by naloxone methiodide or wortmannin pretreatment. The similar pattern of protection was observed in cirrhotic livers. Both intravenous and intrathecal morphine preconditioning protected hepatic architecture much
Release date NZ
January 26th, 2017
Author
Contributor
Created by
Country of Publication
United States
Illustrations
colour illustrations
Imprint
Open Dissertation Press
Dimensions
216x279x11
ISBN-13
9781361292006
Product ID
26644816

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